Recently my laboratory found that the plasma obtained from patients with thrombotic thrombocytopenic purpura (TTP) during fulminant relapse caused the in-vitro aggregation and nucleotide release of washed platelets from normal donor's as well as patients' platelets taken in remission. The platelet aggregability of TTP plasma was diminished when it was preincubated with normal plasma, suggesting there is an inhibitory factor which is deficient in the TTP plasma but present in the normal plasma. Although TTP is a rare disorder, the heretofore underscribed activation and regulation of platelets by factors present in the plasma may have some relevance to other more common vascular disorders, seen as myocardial infarction, stroke, and transient ischemic attack, in which increased platelet reactivity has been described. The objectives of this project are: 1. to characterize the properties of the platelet aggregating factor inhibitor (PAFI) which has already been purified from normal plasma in this laboratory; 2. to develop an immunoassay for the measurement of PAFI in health and diseases such as TTP and other microcirculation disorders; 3. to identify, purify, and characterize platelet aggregating factor (PAF) in the plasma of patients with TTP; 4. to identify the source of PAF; 5. to study the mechanism of inhibition of PAF by PAFI; 6. to study the mechanism of platelet aggregation induced by PAF from TTP plasma and its interaction with receptors of platelet aggregation induced by PAF from TTP plasma or Cohn fraction II and III to produce a PAFI concentrate for the treatment of patients with TTP or TTP-like disorders.